This is the first study to assess the effect of CFBa level within 11 to 17 weeks of gestation on the risk of subsequent GDM. In this study, a propensity score-matched analysis was used, which could balance the distribution of baseline characteristics among groups, reduce the influence of bias and confounding variables in non-random studies and make more reasonable comparison between the experimental group and the control group. Before PSM, the age, family history of diabetes, prepregnancy BMI, reproductive history, ALT, UA, TC, TG, LDL in GDM group were higher than those in normal pregnant group. After PSM, there was no significant difference of the above indexes between the two groups. We found that the levels of CFBa in pregnant women who later developed GDM were significantly higher than those in healthy pregnant women. Logistic regression results confirmed that the level of CFBa was an independent risk factor for the occurrence of GDM. Further grouping according to the quartile of CFBa level, it was found that the incidence of GDM in category 3 was markedly higher than that in the first and the second categories.
At present, insulin resistance and low-grade inflammation caused by immune imbalance are the important reasons for the formation and development of GDM. The chronic inflammation may lead to increased expression of complement gene and activation of complement pathway. Many studies have investigated the role of CFB in metabolic syndrome including type 2 diabetes mellitus, hypertension and insulin resistance. Moreno-navarrete JM et al.  found that the circulating CFB concentration was closely related to IR. The CFB gene expression is highly in omentum tissue, which is positively correlated with BMI, log fasting triglycerides and fasting glucose. Fujita T et al. conducted a study including 32 obese patients with type 2 diabetes mellitus and 32 healthy people showed that the circulating level of CFB was significantly higher in type 2 diabetes mellitus than that in healthy people, and it was also associated with IR, atherosclerosis and diabetic microangiopathy. It is suggested that the activation of the alternative complement pathway can enhance the sustained mild inflammation and insulin resistance, thus inducing the activation of macrophages and accelerating tissue damage. In recent years, an animal experiment was carried out by Coan PM et al. to confirm the role of serum CFB in metabolic syndrome. They knocked out the CFB gene in rats and found that the glucose tolerance and insulin sensitivity of rats were improved. As the activation product of CFB, CFBa has been rarely reported in the population.
GDM can lead to a series of maternal and fetal complications, such as macrosomia, preterm birth and cesarean section. In our study, before PSM, the incidence of macrosomia in GDM group was higher than that in normal pregnant women group (11.25% vs. 4.39%, P = 0.037). After PSM, compared with the normal control group, the amount of postpartum hemorrhage of GDM group was more. The percentage of cesarean section in the GDM group was also higher than that in the normal pregnant women group, but it did not reach statistical significance. This may be due to the psychosocial factors, such as maternal anxiety about delivery or the mother's desire to have cesarean section without any medical indications[24–26], or it may be due to the small sample size of our study.
There are some limitations in the study. First, due to the lack of serum insulin data, it is impossible to calculate the homeostasis model assessment of insulin resistance index (HOMA-IR) and the homeostasis model assessment of beta cell insulin secretion (HOMA-β), so the relationship between CFBa and IR could not be further evaluated. In addition, the sample size of the study was relatively small. More patients are needed to enroll and follow up in the future and confirm these findings.